Pharmacokinetic models are developed for the distribution and disposition of drugs, environmental contaminants, and endogenous metabolites in animals and man. They provide a plausible set of equations that can be used to extrapolate data from animals to man and thereby improve chemotherapy and risk assessment. Emphasis has been placed on regional drug administration, and this has led to the development of spatially distributed models of drug transport in tissue. These analyses have provided considerable insight into the penetration depths of drugs administered intraperitoneally or by infusion into the brain. Pharmacokinetic theory which was developed for intra-arterial drug administration combined with extracorporeal treatment of venous drainage has been further validated in the clinic. Preliminary results have shown the feasibility of documenting appropriate vascular drainage with indocyanine green. Interspecies scaling of regional drug administration has been explored, and a clear allometric basis has been elaborated.